Knockdown of SKA1 gene inhibits cell proliferation and metastasis in human adenoid cystic carcinoma

Zhao, Li; Yang, Hong Li; Li, Ke Yi; Gao, Yue; Dong, Kai; Liu, Zhong hao; Wang, Le xin; Zhang, Bin

doi:10.1016/j.biopha.2017.03.029

Cited by 22 publications

(30 citation statements)

References 35 publications

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“…Another study also demonstrated that knockdown of SKA1 alleviated the activation of ERK1/2 and AKT in bladder cancer cells . In adenoid cystic carcinoma, knockdown of SKA1 inhibited cell proliferation, invasion, and migration, and cell cycle arrest by regulating cell cycle‐promoting genes and the matrix metalloproteinase‐9 gene . These findings suggested that the expression of SKA1 may be induced by cancer‐promoting genes and could contribute to cancer cell aggressiveness and drug resistance.…”

Section: Discussionmentioning

confidence: 87%

“…(46) In adenoid cystic carcinoma, knockdown of SKA1 inhibited cell proliferation, invasion, and migration, and cell cycle arrest by regulating cell cycle-promoting genes and the matrix metalloproteinase-9 gene. (55) These findings suggested that the expression of SKA1 may be induced by cancer-promoting genes and could contribute to cancer cell aggressiveness and drug resistance. Many reports have demonstrated that acquired resistance of RCC cells to molecular targeted therapies induces cancer-promoting genes and activates several alternative pathways.…”

Section: Discussionmentioning

confidence: 94%

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Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma

et al. 2017

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Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA‐10a‐5p (miR‐10a‐5p) was significantly downregulated in RCC specimens. The aims of the present study were to investigate the antitumor roles of miR‐10a‐5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR‐10a‐5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKI). Ectopic expression of miR‐10a‐5p in RCC cell lines (786‐O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore‐associated protein 1 (SKA1) was identified as an antitumor miR‐10a‐5p target by genome‐based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI‐treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR‐10a‐5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR‐10a‐5p and overexpression of the SKA1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 94%

Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma

et al. 2017

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“…Previous studies have shown that SKA1 downregulation suppresses proliferation of bladder cancer and adenoid cystic carcinoma. 27,28 A report also indicated that SKA1 overexpression predicts poor prognosis in HCC. 29 Nevertheless, how SKA1 modulates HCC remains undefined.…”

Section: Discussionmentioning

confidence: 99%

<p>LINC00339 promotes growth and invasiveness of hepatocellular carcinoma by the miR-1182/SKA1 pathway</p>

Xiao¹,

Yu²,

Ma³

2019

OTT

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Background: Extensive research has shown that long noncoding RNA (lncRNA) is involved in tumorigenesis, including hepatocellular carcinoma (HCC). The lncRNA LINC00339 was reported to regulate the development of lung cancer or breast cancer. However, whether LINC00339 participates in HCC progression remains unclear. Here, our results showed that LINC00339 was upregulated in HCC. Methods: qRT-PCR and in situ hybridization (ISH) was used to analyze LINC00339 expression in tumor tissues and cell lines. CCK8 and colony formation assays were used to analyze cell proliferation. Transwell assay was used to analyze cell migration and invasion. Xenograft experiment was used to test tumor growth in vivo. Results: LINC00339 overexpression was correlated with an advanced stage, metastasis, and bad prognosis in HCC patients. Functional investigation showed that LINC00339 knockdown significantly suppressed HCC cell proliferation, migration, and invasion. Moreover, decreased LINC00339 expression inhibited HCC growth in vivo. Mechanistically, LINC00339 could interact with miR-1182 to promote SKA1 expression. We also demonstrated that SKA1 acted as an oncogene and SKA1 upregulation reversed the effect of LINC00339 silencing. Conclusion: Our results illustrated that the LINC00339/miR-1182/SKA1 axis plays an essential role in HCC progression.

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“…The SKA1 complex is a microtubule-binding subcomplex of the outer kinetochore and is essential for proper chromosome segregation (42). Previous data have shown that knockdown of SKA1 inhibits cell proliferation and migration and blocks the cell cycle; moreover, inhibition of SKA1 by small-molecule inhibitors could restrain the activity of the AKT and ERK signaling pathways (43,44). These studies have shown that ZWINT, NDC80, PLK1, SKA1 and Terf/TRIM17 participate in the pathogenesis of malignant neoplasms by affecting mitosis and cell cycle progression, which supports our findings.…”

Section: Discussionmentioning

confidence: 99%

ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion

et al. 2020

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Glioblastoma (GBM) is the most aggressive primary intracranial tumor in adults. Chemoradiotherapy resistance and recurrence after surgery are the main malignant progression factors, leading to a high mortality rate. Therefore, the exploration of novel biomarkers and molecular mechanisms of GBM is urgent. Differentially expressed genes (DEGs) of GBM were screened in a TCGA dataset. Homo sapiens ZW10 interacting kinetochore protein (ZWINT) was found to be upregulated in GBM, which was confirmed by immunohistochemical staining of a tissue microarray. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. A protein-protein interaction (PPI) network was established by the STRING database, and hub genes were visualized by Cytoscape. The correlation results were verified with the GSE15824 dataset. Bioinformatic analysis confirmed that ZWINT was significantly positively correlated with kinetochore protein NDC80 homolog (NDC80), serine/threonine-protein kinase PLK1 (PLK1) and spindle and kinetochore associated complex subunit 1 (SKA1) and together are involved in regulating mitosis and the cell cycle of GBM. ZWINT expression was knocked down in U251 and U87 MG GBM cells by lentiviral vectors carrying a small hairpin RNA (shRNA) targeting ZWINT. The effect of ZWINT silencing on cell proliferation, invasion and apoptosis was determined by the Celigo assay, MTT assay, Transwell assay, flow cytometry and caspase-3/7 assay in vitro. A subcutaneous xenograft tumor model was established to explore the influence of ZWINT knockdown on GBM growth in vivo. Our preliminary study demonstrated that ZWINT knockdown effectively inhibited proliferation and invasion and induced apoptosis of GBM cells and notably suppressed GBM growth in vivo. Therefore, we speculate that ZWINT may be a potential therapeutic biomarker for GBM, with NDC80 and PLK1 conjointly involved in regulating cell division and the mitotic cell cycle.

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Knockdown of SKA1 gene inhibits cell proliferation and metastasis in human adenoid cystic carcinoma

Cited by 22 publications

References 35 publications

Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma

Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5p in renal cell carcinoma

<p>LINC00339 promotes growth and invasiveness of hepatocellular carcinoma by the miR-1182/SKA1 pathway</p>

ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion

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